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Made available in DSpace on 2018-12-11T17:21:56Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-06-01. Added 1 bitstream(s) on 2019-10-09T18:31:56Z : No. of bitstreams: 1 S2359-39972018000300366.pdf: 123932 bytes, checksum: 884f7b3ea5771ca0dc08ec15ac8f5036 (MD5) Made available in DSpace on 2018-12-11T17:21:56Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-06-01. Added 1 bitstream(s) on 2019-10-09T18:31:56Z : No. of bitstreams: 1 S2359-39972018000300366.pdf: 123932 bytes, checksum: 884f7b3ea5771ca0dc08ec15ac8f5036 (MD5) Made available in DSpace on 2018-12-11T17:21:56Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-06-01. Added 1 bitstream(s) on 2019-10-09T18:31:56Z : No. of bitstreams: 1 S2359-39972018000300366.pdf: 123932 bytes, checksum: 884f7b3ea5771ca0dc08ec15ac8f5036 (MD5) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Objective: Graves’ ophthalmopathy (GO) is an autoimmune disease that leads to ocular proptosis caused by fat accumulation and inflammation, and the main treatment is corticosteroid therapy. Retinoid acid receptor-alpha (RARα) seems to be associated with inflammation and adipocyte differentiation. This study aimed to assess the effect of glucocorticoid treatment on orbital fibroblasts of GO patient treated or not with different glucocorticoid doses. Materials and methods: Orbital fibroblasts collected during orbital decompression of a female patient with moderately severe/severe GO were cultivated and treated with 10 nM and 100 nM dexamethasone (Dex). RARα gene expression in the treated and untreated cells was then compared. Results: Fibroblast RARα expression was not affected by 100 nM Dex. On the other hand, RARα expression was 24% lower in cells treated with 10 nM Dex (p < 0.05). Conclusions: Orbital fibroblasts from a GO patient expressed the RARα gene, which was unaffected by higher, but decreased with lower doses of glucocorticoid. Divisão de Endocrinologia Departamento de Medicina Interna Faculdade de Medicina de Botucatu Universidade Estadual de São Paulo (Unesp) Instituto Federal de Educação Ciência e Tecnologia do Estado de São Paulo (IFSP) Departamento de Oftalmologia Otorrinolaringologia e Cirurgia de Cabeça e Pescoço Faculdade de Medicina de Botucatu Universidade Estadual de São Paulo (Unesp) Divisão de Endocrinologia Departamento de Medicina Interna Faculdade de Medicina de Botucatu Universidade Estadual de São Paulo (Unesp) Departamento de Oftalmologia Otorrinolaringologia e Cirurgia de Cabeça e Pescoço Faculdade de Medicina de Botucatu Universidade Estadual de São Paulo (Unesp) FAPESP: #:03/03651-0 FAPESP: 2011/18464-8

Obesity is characterised by chronic low-grade inflammation, and lycopene has been reported to display anti-inflammatory effects. However, it is not clear whether lycopene supplementation modulates adipokine levelsin vivoin obesity. To determine whether lycopene supplementation can regulate adipokine expression in obesity, male Wistar rats were randomly assigned to receive a control diet (C,n6) or a hyperenergetic diet (DIO,n12) for 6 weeks. After this period, the DIO animals were randomised into two groups: DIO (n6) and DIO supplemented with lycopene (DIO+L,n6). The animals received maize oil (C and DIO) or lycopene (DIO+L, 10 mg/kg body weight (BW) per d) by oral administration for a 6-week period. The animals were then killed by decapitation, and blood samples and epididymal adipose tissue were collected for hormonal determination and gene expression evaluation (IL-6, monocyte chemoattractant protein-1 (MCP-1),TNF-α, leptin and resistin). There was no detectable lycopene in the plasma of the C and DIO groups. However, the mean lycopene plasma concentration was 24 nmol in the DIO+L group. Although lycopene supplementation did not affect BW or adiposity, it significantly decreased leptin, resistin andIL-6gene expression in epididymal adipose tissue and plasma concentrations. Also, it significantly reduced the gene expression ofMCP-1in epididymal adipose tissue. Lycopene affects adipokines by reducing leptin, resistin and plasma IL-6 levels. These data suggest that lycopene may be an effective strategy in reducing inflammation in obesity.

The purpose of this study it was to evaluate the frequency of Multiple Endocrine Neoplasia type 1 (MEN1) in patients with pituitary adenoma and to perform genetic analysis and familial screening of those individuals afflicted with MEN1. 144 patients with pituitary adenoma at Botucatu Medical School, UNESP—Univ Estadual Paulista, were assessed retrospectively for MEN1 during the years of 2005–2011. The patients were evaluated for the presence of primary hyperparathyroidism (PHP) and enteropancreatic tumors. Genetic analysis was performed for the individuals with clinically diagnosed MEN1. Thirteen patients met the diagnostic criteria for MEN1, but three individuals belong to the same family and they were considered as a single MEN1 event, revealing 7.7 % frequency of MEN1 in this patient group. Genetic analysis showed MEN1 mutations in four index cases: IVS4+1 G>A, IVS3-6 C>T, c.1547insC and a new D180A mutation. One patient did not agree to participate in the genetic study and another one was referred for follow up in other hospital. Only polymorphisms were found in the other individuals, one of which was novel. We identified a high frequency of MEN1 in pituitary adenoma patients. Since PHP is one of the most common MEN1 tumor and patients are mostly asymptomatic, we suggest that all pituitary adenoma patients have their calcium profile analyzed.

Made available in DSpace on 2018-12-11T17:29:34Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-08-01. Added 1 bitstream(s) on 2019-10-09T18:32:39Z : No. of bitstreams: 1 S1807-59322016000800470.pdf: 341861 bytes, checksum: 531786629f0ab751fa3f3a1b78516fec (MD5) OBJECTIVE: The aim of this study was to evaluate the roles of the Taql and Bsml vitamin D receptor gene polymorphisms in hospital mortality of burn patients. METHODS: In total, 105 consecutive burn injury patients over 18 years in age who were admitted to the Burn Unit of Bauru State Hospital from January to December 2013 were prospectively evaluated. Upon admission, patient demographic information was recorded and a blood sample was taken for biochemical analysis to identify the presence of the Taql(rs731236) and Bsml(rs1544410) polymorphisms. All of the patients were followed over their hospital stay and mortality was recorded. RESULTS: Eighteen of the patients did not sign the informed consent form, and there were technical problems with genotype analysis for 7 of the patients. Thus, 80 patients (mean age, 42.5�16.1 years) were included in the final analysis. In total, 60% of the patients were male, and 16.3% died during the hospital stay. The genotype frequencies for the Taql polymorphism were 51.25% TT, 41.25% TC and 7.50% CC; for the Bsml polymorphism, they were 51.25% GG, 42.50% GA and 6.25% AA. In logistic regression analysis, after adjustments for age, gender and total body surface burn area, there were no associations between the Taql (OR: 1.575; CI95%: 0.148- 16.745; p=0.706) or Bsml (OR: 1.309; CI95%: 0.128-13.430; p=0.821) polymorphisms and mortality for the burn patients. CONCLUSIONS: Our results suggest that the Taql and Bsml vitamin D receptor gene polymorphisms are not associated with hospital mortality of burn patients. Universidade Estadual Paulista – UNESP Faculdade de Medicina de Botucatu Departamento de Medicina Interna Instituto Federal S�o Paulo – IFSP, Campus S�o Roque Universidade Estadual Paulista – UNESP Faculdade de Medicina de Botucatu Departamento de Medicina Interna

OBJETIVO: Verificar o perfil dos hormônios tireóideos (HTs) em pacientes pós-menopausa portadoras de carcinoma de mama (CaM). SUJEITOS E MÉTODOS: Participaram 12 pacientes com CaM em estádio I ou II sem intervenções que pudessem interferir na progressão tumoral e um grupo controle com 18 pacientes em pós-menopausa sem CaM. Foram dosados os níveis séricos de anticorpo antitiroperoxidase (TPOAB), hormônio estimulante da tireoide (TSH), tiroxina livre (T4L), estradiol (E2), hormônio folículo estimulante (FSH) e hormônio luteinizante (LH) antes e após a cirurgia, e realizada a imunoistoquímica dos receptores de estrógeno (ER) e progesterona (PR). RESULTADOS: Quatro pacientes com CaM apresentaram alterações do perfil hormonal tireoidiano: dois hipertireoidismo, um hipotireoidismo e positividade TPO-AB, todas com ER e PR positivos. Os níveis de TSH dessas pacientes não foram diferentes dos níveis encontrados no grupo controle (1,89 ± 1,56 vs. 2,86 ± 3,12 mUI/mL), porém os níveis de T4L nas pacientes com CaM foram estatisticamente maiores que o controle (1,83 ± 0,57 vs. 1,10 ± 0,20 ng/dL). CONCLUSÃO: Esses resultados reforçam a necessidade de avaliação do status tireoidiano em pacientes com CaM, uma vez que, na ausência de E2, mudanças clínicas nos HTs podem atuar em vias controladas pelo E2. OBJECTIVE: The aim of this study was to determine thyroid hormone (TH) profile in postmenopausal patients with breast cancer (BC). SUBJECTS AND METHODS: 12 CaM patients stages I or II, without interventions that could interfere with tumor progression were selected, as well as and a control group with 18 postmenopausal women without CaM. We measured serum anti-thyroperoxidase antibody (TPOAB), thyroid-stimulating hormone (TSH), free thyroxine (T4L), estradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH), before and after surgery, besides immunohistochemistry for estrogen (ER) and progesterone (PR) receptors. RESULTS: Four patients with CaM showed changes in thyroid hormone profile: two had hyperthyroidism, one hypothyroidism, and one was positive for TPO-AB. All of them positive for ER and PR. TSH levels in breast cancer patients were not different from levels found in the control group (1.89 ± 1.56 vs. 2.86 ± 3.12 mIU/mL), but the levels of T4L in patients with CaM were statistically higher than those of the control group (1.83 ± 0.57 vs. 1.10 ± 0.20 ng/dL). CONCLUSION: These results reinforce the need for assessment of thyroid status in CaM patients, since in the absence of E2, changes in clinical HTs can act in E2-controlled processes.

Obesity has become a major public health problem, most commonly treated via dietary restriction to promote weight loss. Although leptin and thyroid hormones are involved in the regulation of energy balance, the role of these hormones after the stabilization of weight loss remains unclear. This study was designed to analyze the effect of thyroid hormone on sustained weight loss and leptin gene expression in obese animals after a loss of 5% to 10% of body weight. Thirty-day–old male Wistar rats were separated into 4 groups: control, obese, calorie restriction (CR), and calorie restriction with triiodothyronine administration (CRT). The obese group had increased weight and adiposity, leptin and insulin levels, and leptin gene expression. Dietary restriction in the CR group resulted in decreased body weight and adiposity, diminished leptin, and increased thyroid hormone receptor β expression. The CRT group, submitted to dietary restriction with concomitant administration of a physiologic triiodothyronine dose, had thyroid hormone receptor β expression at levels comparable with those observed in the control group and simultaneously increased leptin expression as compared with that in the CR group, suggesting that thyroid hormone modulates leptin expression under conditions of calorie restriction. Increased leptin expression in the CRT group did not result in increased circulating leptin or a statistically significant reduction in body weight during the treatment period. These data provide impetus for further study, as a longer treatment period may result in increased circulating leptin and, thus, further reduction in body weight during calorie restriction in an obesity model.

Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2013-08-22T19:00:46Z No. of bitstreams: 1 S0004-27302009000700010.pdf: 407116 bytes, checksum: 5232c39db44222e730a2a05667580769 (MD5) Made available in DSpace on 2013-08-22T19:00:46Z (GMT). No. of bitstreams: 1 S0004-27302009000700010.pdf: 407116 bytes, checksum: 5232c39db44222e730a2a05667580769 (MD5) Previous issue date: 2009-10-01 Made available in DSpace on 2013-09-30T19:59:43Z (GMT). No. of bitstreams: 2 S0004-27302009000700010.pdf: 407116 bytes, checksum: 5232c39db44222e730a2a05667580769 (MD5) S0004-27302009000700010.pdf.txt: 25798 bytes, checksum: f33d537c830cae4b3c1f89475540ec2b (MD5) Previous issue date: 2009-10-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T13:47:47Z No. of bitstreams: 2 S0004-27302009000700010.pdf: 407116 bytes, checksum: 5232c39db44222e730a2a05667580769 (MD5) S0004-27302009000700010.pdf.txt: 25798 bytes, checksum: f33d537c830cae4b3c1f89475540ec2b (MD5) Made available in DSpace on 2014-05-20T13:47:47Z (GMT). No. of bitstreams: 2 S0004-27302009000700010.pdf: 407116 bytes, checksum: 5232c39db44222e730a2a05667580769 (MD5) S0004-27302009000700010.pdf.txt: 25798 bytes, checksum: f33d537c830cae4b3c1f89475540ec2b (MD5) Previous issue date: 2009-10-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) OBJETIVO: Para compreender melhor a ação da triiodotironina (T3) agonista de estrógeno (E2), foram comparados os efeitos destes hormônios em células de câncer de mama MDA-MB-231 ER negativas com um clone de MDA-MB-231, transfectado estavelmente com o cDNA de ERα (S30), em termos de proliferação e modulação dos receptores hormonais. RESULTADOS: Experimentos de crescimento mostraram que MDA-MB-231 não foi modulada por qualquer hormônio ou pelo tamoxifeno (TAM). O crescimento de S30 foi essencialmente inalterado por tratamento com E2 10-9M ou 10-8M, mas T3 10-8M inibiu significativamente a proliferação quando comparada a ambas concentrações de E2. Esse efeito não foi revertido pelo TAM, sugerindo um resultado não genômico, independente de ERE. Tratamentos com 10-8M de E2 ou de T3 reduziram a expressão do gene ERα em S30, efeito parcialmente impedido pela associação com TAM, sem efeito na expressão de TR. Os resultados sugerem que, em S30, T3 10-8M tem ação semelhante ao E2 com relação à modulação do gene ERα. CONCLUSÕES: Esses resultados enfatizam a necessidade de dosagem de T3 circulante antes da introdução do tratamento antiestrogênico no câncer de mama. OBJECTIVE: To better understand the estrogen (E2) agonist action of triiodothyronine (T3) the effects of these hormones on ER negative MDA-MB-231 breast cancer cells were compared with those on S30, a clone of MDA-MB-231 stably transfected with ERα cDNA, in terms of proliferation and modulation of hormone receptors. RESULTS: Growth experiments showed that MDA-MB-231 was not modulated by any hormone or tamoxifen (TAM). Treatment with E2, 10-8M or 10-9M had little effect on S30 proliferation. T3 at 10-8M significantly inhibited proliferation. This effect was not reverted by TAM. Treatments with 10-8M concentration of E2 or T3 reduced ERα gene expression in S30, an effect partially blocked by association with TAM, with no effect on TR expression. These results suggest that, in S30, 10-8M T3 has a similar action to E2 relative to ERα gene modulation. CONCLUSIONS: Such results emphasize the need of determining T3 levels, before the introduction of antiestrogenic forms of treatment in breast cancer patients. Universidade Estadual Paulista Júlio de Mesquista Filho Departamento de Clínica Médica Universidade de São Paulo Faculdade de Medicina Departamento de Radiologia Unesp Instituto de Ciências Biológicas Departamento de Bioestatística Universidade Estadual Paulista Júlio de Mesquista Filho Departamento de Clínica Médica Unesp Instituto de Ciências Biológicas Departamento de Bioestatística

Mutations in biochemical pathways mediators are often found in cancer, and it is observed that via phosphoinositide 3-kinase (PI3K) is associated with tumor development and progression. This pathway is involved in several metabolic processes, including regulation of gene expression by non-classical actions of thyroid hormone. The objective of this paper is to provide a brief literature review of progress in information obtained on the PI3K on the last fifteen years. It was used the PubMed database, with the assistance of MeSh (Medical Subject Headings) and as descriptor "Phosphoinositide 3-Kinase" AND "Thyroid Hormones" to the selection of base articles, and later were included references found in those to complement the review. It stands between the information obtained from them that PI3Ks are lipid kinases that phosphorylate the 3-OH group of moderatory inositol molecules of cellular functions regulatory proteins. The PI3K pathway is involved in a wide variety of cellular processes, including intracellular traffic, cytoskeletal organization, apoptosis prevention, cell growth and transformation and it is important for various cell lineages differentiation. This pathway inhibitors promoted multiple possibilities of experiments, which led to the discovery of a relationship between PI3K pathway and other proteins such as protein kinase B (also known as AKT), mammalian target of rapamycin (mTOR) and oncoprotein RAS. The via was also associated with the expression of cancer related genes and hormones, including thyroid hormone. Thyroid hormones (TH) can work by other mechanisms besides the classical pathway, which occurs through receptors and responsive elements. The alternative to it is the non-classical or non-genomic pathway, in which TH activates PI3K, either by binding to TRβ or to αvβ3 integrin. This activation results in the transcription of specific genes, such as hypoxia inducing factor (HIF-1α) glucose transporter 1 (GLUT1), calcineurin inhibitor (ZAKI4α), among others.

Made available in DSpace on 2015-02-02T12:39:34Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-10-01Bitstream added on 2015-02-02T13:07:53Z : No. of bitstreams: 1 S0004-27492014000500339.pdf: 579808 bytes, checksum: e8fd687573ee4954ed41efeed3136c7f (MD5) Made available in DSpace on 2015-02-02T12:39:34Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-10-01Bitstream added on 2015-02-02T13:07:53Z : No. of bitstreams: 1 S0004-27492014000500339.pdf: 579808 bytes, checksum: e8fd687573ee4954ed41efeed3136c7f (MD5) Made available in DSpace on 2015-02-02T12:39:34Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-10-01Bitstream added on 2015-02-02T13:07:53Z : No. of bitstreams: 1 S0004-27492014000500339.pdf: 579808 bytes, checksum: e8fd687573ee4954ed41efeed3136c7f (MD5) Made available in DSpace on 2015-02-02T12:39:34Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-10-01Bitstream added on 2015-02-02T13:07:53Z : No. of bitstreams: 1 S0004-27492014000500339.pdf: 579808 bytes, checksum: e8fd687573ee4954ed41efeed3136c7f (MD5) Made available in DSpace on 2015-02-02T12:39:34Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-10-01Bitstream added on 2015-02-02T13:07:53Z : No. of bitstreams: 1 S0004-27492014000500339.pdf: 579808 bytes, checksum: e8fd687573ee4954ed41efeed3136c7f (MD5) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Universidade Estadual Paulista Botucatu Medical School Internal Medicine Department Universidade Estadual Paulista Botucatu Medical School Ophthalmology, Otorhinolaryngology and Head and Neck Department Universidade Estadual Paulista Botucatu Medical School Internal Medicine Department Universidade Estadual Paulista Botucatu Medical School Ophthalmology, Otorhinolaryngology and Head and Neck Department

Made available in DSpace on 2015-08-26T19:19:03Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-06-01. Added 1 bitstream(s) on 2015-08-31T13:05:04Z : No. of bitstreams: 1 S2359-39972015000300273.pdf: 130120 bytes, checksum: 6dc2ae5dfe61f973ea9aecc7248da395 (MD5) Made available in DSpace on 2015-08-26T19:19:03Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-06-01. Added 1 bitstream(s) on 2015-08-31T13:05:04Z : No. of bitstreams: 1 S2359-39972015000300273.pdf: 130120 bytes, checksum: 6dc2ae5dfe61f973ea9aecc7248da395 (MD5) Made available in DSpace on 2015-08-26T19:19:03Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-06-01. Added 1 bitstream(s) on 2015-08-31T13:05:04Z : No. of bitstreams: 1 S2359-39972015000300273.pdf: 130120 bytes, checksum: 6dc2ae5dfe61f973ea9aecc7248da395 (MD5) Made available in DSpace on 2015-08-26T19:19:03Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-06-01. Added 1 bitstream(s) on 2015-08-31T13:05:04Z : No. of bitstreams: 1 S2359-39972015000300273.pdf: 130120 bytes, checksum: 6dc2ae5dfe61f973ea9aecc7248da395 (MD5) Made available in DSpace on 2015-08-26T19:19:03Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-06-01. Added 1 bitstream(s) on 2015-08-31T13:05:04Z : No. of bitstreams: 1 S2359-39972015000300273.pdf: 130120 bytes, checksum: 6dc2ae5dfe61f973ea9aecc7248da395 (MD5) Graves’ ophthalmopathy (GO) is one of the most severe clinical manifestations of Graves’ disease (GD), and its treatment might involve high-dose glucocorticoid therapy. The higher incidence of GO among females, and the reported association between polymorphisms of estrogen receptor (ER) and GD susceptibility have led us to question the role of estrogen and its receptor in GO pathogenesis. We, thus, assessed estrogen receptor-alpha (ERA) gene expression in cultures of orbital fibroblasts from a patient with GO before (controls) and after treatment with 10 nM and 100 nM dexamethasone (DEX). Orbital fibroblasts showed ERA gene expression. In the cells treated with 10 nM and 100 nM DEX, ERA gene expression was, respectively, 85% higher and 74% lower, than in the control group. We concluded that ERA gene expression is found in the orbital fibroblasts of patient with GO, which may be affected by glucocorticoids in a dose-related manner. Arch Endocrinol Metab. 2015;59(3):273-6 Sao Paulo State University Botucatu Medical School Internal Medicine Department Unesp Sao Paulo State University Botucatu Medical School Internal Medicine Department Unesp

PCR, or “polymerase chain reaction”, is one of most useful techniques in genomics research. High quality DNA extraction is necessary to obtain satisfactory results. Some methods utilized to obtain DNA from blood include a simple salting-out procedure for extracting DNA from human nucleated cells. This method is widely used by many laboratories because it can obtain DNA with sufficient quality to realize PCR, using materials that do not pose risk to researchers and is more cost-efficient than other approaches. Although salting-out has spread to many laboratories, its protocols do not highlight technical details of their steps that could affect final DNA quality and, for this reason, underwent some modifications in this work in order to obtain an efficient extraction. We used 2 to 4 mL of blood for each of 30 DNA samples. For the supernatant step in first EDTA wash, we established a subtraction pattern from 15 mL to 2.5 mL, independently of initial sample volume of blood, to avoid losing leucocytes. The num...

Amphiregulin (AREG) is considered an oncogene whose expression is related to several types of cancer. Our group identified a triiodothyronine (T3) action on different genes of breast cancer cell li...

The thyroid hormones (THs), triiodothyronine (T3) and thyroxine (T4), are essential for survival; they are involved in the processes of development, growth, and metabolism. In addition to hyperthyroidism or hypothyroidism, THs are involved in other diseases. The role of THs in the development and differentiation of mammary epithelium is well established; however, their specific role in the pathogenesis of breast cancer (BC) is controversial. Steroid hormones affect many human cancers and the abnormal responsiveness of the mammary epithelial cells to estradiol (E2) in particular is known to be an important cause for the development and progression of BC. The proliferative effect of T3 has been demonstrated in various types of cancer. In BC cell lines, T3 may foster the conditions for tumor proliferation and increase the effect of cell proliferation by E2; thus, T3 may play a role in the development and progression of BC. Studies show that T3 has effects similar to E2 in BC cell lines. Despite controversy regarding the relationship between thyroid disturbances and the incidence of BC, studies show that thyroid status may influence the development of tumor, proliferation and metastasis.

Made available in DSpace on 2015-12-07T15:30:30Z (GMT). No. of bitstreams: 0 Previous issue date: 2014. Added 1 bitstream(s) on 2015-12-07T15:52:57Z : No. of bitstreams: 1 PMC3950583.pdf: 2375661 bytes, checksum: fa0182a0b8ea0d24d60647be62a0a9d1 (MD5) We investigated thyroid hormone levels in menopausal BrC patients and verified the action of triiodothyronine on genes regulated by estrogen and by triiodothyronine itself in BrC tissues. We selected 15 postmenopausal BrC patients and a control group of 18 postmenopausal women without BrC. We measured serum TPO-AB, TSH, FT4, and estradiol, before and after surgery, and used immunohistochemistry to examine estrogen and progesterone receptors. BrC primary tissue cultures received the following treatments: ethanol, triiodothyronine, triiodothyronine plus 4-hydroxytamoxifen, 4-hydroxytamoxifen, estrogen, or estrogen plus 4-hydroxytamoxifen. Genes regulated by estrogen (TGFA, TGFB1, and PGR) and by triiodothyronine (TNFRSF9, BMP-6, and THRA) in vitro were evaluated. TSH levels in BrC patients did not differ from those of the control group (1.34 ± 0.60 versus 2.41 ± 1.10 μ U/mL), but FT4 levels of BrC patients were statistically higher than controls (1.78 ± 0.20 versus 0.95 ± 0.16 ng/dL). TGFA was upregulated and downregulated after estrogen and triiodothyronine treatment, respectively. Triiodothyronine increased PGR expression; however 4-hydroxytamoxifen did not block triiodothyronine action on PGR expression. 4-Hydroxytamoxifen, alone or associated with triiodothyronine, modulated gene expression of TNFRSF9, BMP-6, and THRA, similar to triiodothyronine treatment. Thus, our work highlights the importance of thyroid hormone status evaluation and its ability to interfere with estrogen target gene expression in BrC samples in menopausal women. Department of Biological Science, São Paulo Federal Institute (IFSP), 18136-540 São Roque, SP, Brazil ; Department of Internal Medicine, Division of Endocrinology and Metabolism, UNESP, 18618-000 Botucatu, SP, Brazil. Department of Internal Medicine, Division of Endocrinology and Metabolism, UNESP, 18618-000 Botucatu, SP, Brazil. Department of Biological Science, São Paulo Federal Institute (IFSP), 18136-540 São Roque, SP, Brazil ; Department of Internal Medicine, Division of Endocrinology and Metabolism, UNESP, 18618-000 Botucatu, SP, Brazil. Department of Internal Medicine, Division of Endocrinology and Metabolism, UNESP, 18618-000 Botucatu, SP, Brazil.

Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:30:42Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:38:01Z : No. of bitstreams: 1 2-s2.0-84884264499.pdf: 942276 bytes, checksum: 17045a1e8ee4d958b7e3d559fc56068d (MD5) Made available in DSpace on 2014-05-27T11:30:42Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-09-18 The present study aimed to examine the effects of thyroid hormone (TH), more precisely triiodothyronine (T3), on the modulation of leptin mRNA expression and the involvement of the phosphatidyl inositol 3 kinase (PI3K) signaling pathway in adipocytes, 3T3-L1, cell culture. We examined the involvement of this pathway in mediating TH effects by treating 3T3-L1 adipocytes with physiological (P=10nM) or supraphysiological (SI=100 nM) T3 dose during one hour (short time), in the absence or the presence of PI3K inhibitor (LY294002). The absence of any treatment was considered the control group (C). RT-qPCR was used for mRNA expression analyzes. For data analyzes ANOVA complemented with Tukey's test was used at 5% significance. T3 increased leptin mRNA expression in P (2.26 ± 0.36, p< 0.001), SI (1.99 ±0.22, p< 0.01) compared to C group (1± 0.18). This increase was completely abrogated by LY294002 in P (1.31±0.05, p< 0.001) and SI (1.33±0.31, p< 0.05). Western blotting confirmed these results at protein level, indicating the PI3K pathway dependency. To examine whether leptin is directly induced by T3, we used the translation inhibitor cycloheximide (CHX). In P, the presence of CHX maintained the levels mRNA leptin, but was completely abrogated in SI (1.14±0.09, p> 0.001). These results demonstrate that the activation of the PI3K signaling pathway has a role in TH-mediated direct and indirect leptin gene expression in 3T3-L1 adipocytes. © 2013 Oliveira et al. Department of Internal Medicine Botucatu School of Medicine University of São Paulo State (UNESP), Botucatu, São Paulo Department of Physiology Federal University of São Paulo (UNIFESP), São Paulo Department of Internal Medicine Botucatu School of Medicine University of São Paulo State (UNESP), Botucatu, São Paulo

This study aimed evaluate whether estrogen modulates amphiregulin (AREG) gene expression in breast tumor cells. For this, MCF-7 cells were treated for 1 or 4 hours with estrogen (E2 10−7 M) in the ...

Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:28:33Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:32:18Z : No. of bitstreams: 1 2-s2.0-84874511518.pdf: 447094 bytes, checksum: b79744f190efab28202a9a9e0a1d266c (MD5) Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:28:33Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:32:18Z : No. of bitstreams: 1 2-s2.0-84874511518.pdf: 447094 bytes, checksum: b79744f190efab28202a9a9e0a1d266c (MD5) Made available in DSpace on 2014-05-27T11:28:33Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-02-28 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:28:33Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:32:18Z : No. of bitstreams: 1 2-s2.0-84874511518.pdf: 447094 bytes, checksum: b79744f190efab28202a9a9e0a1d266c (MD5) Made available in DSpace on 2014-05-27T11:28:33Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-02-28 Made available in DSpace on 2014-05-27T11:28:33Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-02-28 Made available in DSpace on 2014-05-27T11:28:33Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-02-28 This study was designed to determine the genotoxicity of a supraphysiological dose of triiodothyronine (T3) in both obese and calorie-restricted obese animals. Fifty male Wistar rats were randomly assigned to one of the two following groups: control (C; n = 10) and obese (OB; n = 40). The C group received standard food, whereas the OB group was fed a hypercaloric diet for 20 weeks. After this period, half of the OB animals (n = 20) were subjected to a 25%-calorie restriction of standard diet for 8 weeks forming thus a new group (OR), whereas the remaining OB animals were kept on the initial hypercaloric diet. During the following two weeks, 10 OR animals continued on the calorie restriction diet, whereas the remaining 10 rats of this group formed a new group (ORS) given a supraphysiological dose of T3 (25 μg/100 g body weight) along with the calorie restriction diet. Similarly, the remaining OB animals were divided into two groups, one that continued on the hypercaloric diet (OB, n = 10), and one that received the supraphysiological dose of T3 (25 μg/100 g body weight) along with the hypercaloric diet (OS, n = 10) for two weeks. The OB group showed weight gain, increased adiposity, insulin resistance, increased leptin levels and genotoxicity; T3 administration in OS animals led to an increase in genotoxicity and oxidative stress when compared with the OB group. The OR group showed weight loss and normalized levels of adiposity, insulin resistance, serum leptin and genotoxicity, thus having features similar to those of the C group. On the other hand, the ORS group, compared to OR animals, showed higher genotoxicity. Our results indicate that regardless of diet, a supraphysiological dose of T3 causes genotoxicity and potentiates oxidative stress. © 2013 de Sibio et al. Department of Internal Medicine Botucatu Medical School - University of Sao Paulo State (UNESP), Botucatu, SP Department of Pathology Botucatu Medical School - University of Sao Paulo State (UNESP), Botucatu, SP Department of Biostatistics Biosciences Institute - University of Sao Paulo State (UNESP), Botucatu, SP Department of Internal Medicine Botucatu Medical School - University of Sao Paulo State (UNESP), Botucatu, SP Department of Pathology Botucatu Medical School - University of Sao Paulo State (UNESP), Botucatu, SP Department of Biostatistics Biosciences Institute - University of Sao Paulo State (UNESP), Botucatu, SP

Made available in DSpace on 2016-04-01T18:44:23Z (GMT). No. of bitstreams: 0 Previous issue date: 2013. Added 1 bitstream(s) on 2016-04-01T18:49:52Z : No. of bitstreams: 1 ISSN0004-2730-2013-57-05-368-374.pdf: 218443 bytes, checksum: 5474d376f1638e12ee42afe0365fd7b3 (MD5) Objetivo: Examinar o efeito de diferentes doses de triiodotironina (T3) sobre a expressão gênica dos receptores TRα e TRβ em diferentes tempos. Materiais e métodos: Adipócitos, 3T3-L1, foram incubados com T3 nas doses fisiológica (F, 10nM) e suprafisiológicas (SI, 100nM ou SII, 1000nM) ou veículo (controle, C) durante 0,5, 1, 6 ou 24h. mRNA dos TRs foram detectados utilizando PCR em tempo real. Resultados: Níveis de TRβ aumentaram em F em 0,5h. Após 1h, níveis de TRα aumentaram em F e SI comparado ao C, enquanto TRβ diminuiu no SII comparado com C, F, e SI. Após 6h, ambos os genes foram suprimidos em todas concentrações. Em 24h, níveis de TRα e TRβ retornaram aos do C. Conclusões: Ação do T3 em F iniciou-se em 1h para TRα e 0,5h para TRβ. Esses resultados são importantes para determinar tempo inicial e dose de T3 em que os receptores de HT são ativados em adipócitos. Objective: To examine the effect of different doses of triiodothyronine (T3) on mRNA levels of thyroid hormone receptors, TRα and TRβ, at different times. Materials and methods: 3T3-L1 adipocytes were incubated with T3 (physiological dose: F; supraphysiological doses: SI or SII), or without T3 (control, C) for 0.5, 1, 6, or 24h. TRα and TRβ mRNA was detected using real-time polymerase chain reaction. Results: F increased TRβ mRNA levels at 0.5h. After 1h, TRα levels increased with F and SI and TRβ levels decreased with SII compared with C, F, and SI. After 6h, both genes were suppressed at all concentrations. In 24h, TRα and TRβ levels were similar to those of C group. Conclusions: T3 action with F began at 1h for TRα and at 0.5h for TRβ. These results suggest the importance of knowing the times and doses that activate T3 receptors in adipocytes. Department of Physiology, São Paulo Federal University (Unifesp), São Paulo, SP, Brazil Department of Internal Clinic, Botucatu Medicine School, São Paulo State University (Unesp), Botucatu, SP, Brazil Department of Biostatistics, Biosciences Institute, Unesp, Botucatu, SP, Brazil

Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2013-08-22T19:03:19Z No. of bitstreams: 1 S0004-27302012000800018.pdf: 138617 bytes, checksum: 6272e3edefd445c844169dd6dec96675 (MD5) Made available in DSpace on 2013-08-22T19:03:19Z (GMT). No. of bitstreams: 1 S0004-27302012000800018.pdf: 138617 bytes, checksum: 6272e3edefd445c844169dd6dec96675 (MD5) Previous issue date: 2012-11-01 Made available in DSpace on 2013-09-30T20:05:05Z (GMT). No. of bitstreams: 2 S0004-27302012000800018.pdf: 138617 bytes, checksum: 6272e3edefd445c844169dd6dec96675 (MD5) S0004-27302012000800018.pdf.txt: 14858 bytes, checksum: f0c885a3c1b012752d54dfd77f638c28 (MD5) Previous issue date: 2012-11-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T15:16:41Z No. of bitstreams: 2 S0004-27302012000800018.pdf: 138617 bytes, checksum: 6272e3edefd445c844169dd6dec96675 (MD5) S0004-27302012000800018.pdf.txt: 14858 bytes, checksum: f0c885a3c1b012752d54dfd77f638c28 (MD5) Made available in DSpace on 2014-05-20T15:16:41Z (GMT). No. of bitstreams: 2 S0004-27302012000800018.pdf: 138617 bytes, checksum: 6272e3edefd445c844169dd6dec96675 (MD5) S0004-27302012000800018.pdf.txt: 14858 bytes, checksum: f0c885a3c1b012752d54dfd77f638c28 (MD5) Previous issue date: 2012-11-01 A osteomalacia oncogênica é um diagnóstico clínico desafiador, caracterizado pela perda renal de fosfato e baixos níveis de 1,25-di-hidroxivitamina D3, ocorrendo na presença de um tumor produtor de altos níveis de fator de crescimento de fibroblasto 23. No entanto, é possível que se trate muito mais de uma falha de diagnóstico clínico do que propriamente uma doença rara. Os autores relatam o caso de um homem de 42 anos com histórico de fraqueza muscular progressiva por cinco anos e restrição à cadeira de rodas, sem diagnóstico. Seus exames laboratoriais evidenciavam baixos níveis de fósforo. A remoção cirúrgica de um hemangiopericitoma detectado previamente em cavidade nasal levou à resolução completa dos sintomas. Os autores enfatizam que, mesmo com a etiologia já evidenciada, o paciente consultou diversos clínicos no decorrer dos cinco anos até que fossem instituídos o diagnóstico e o tratamento adequados. Arq Bras Endocrinol Metab. 2012;56(8):570-3 Diagnosing oncogenic osteomalacia is still a challenge. The disorder is characterized by osteomalacia caused by renal phosphate wasting and low serum concentration of 1,25-dihydroxyvitamin D3 occurring in the presence of a tumor that produces high levels of fibroblast growth factor 23. However, it is possible that the disease is much more misdiagnosed than rare. We present the case of a 42-year-old man with a long-term history of undiagnosed progressive muscle weakness. His laboratory results mainly showed low serum phosphate. Surgical removal of a nasal hemangiopericytoma that had been diagnosed five years earlier, brought him to a symptom-free condition. Even though knowing the underlying etiology would explain his osteomalacia, the patient sought medical help from countless physicians for five consecutive years, and only after adequate treatment a rewarding outcome was achieved. Arq Bras Endocrinol Metab. 2012;56(8):570-3 Universidade Estadual de São Paulo Faculdade de Medicina de Botucatu Department of Medicine Universidade Federal de São Paulo (UNIFESP) Department of Neurology and Neurosurgery Metabolism and Molecular Medicine Northwestern University Division of Endocrinology

The primary function of adipose tissue is storing energy in triacylglycerol (TG) form, neutralizing the excess of circulating lipids and saving non-adipose tissues of a fat overload. Under normal conditions, in the postprandial state, there is lipogenic endocrine system stimulation, allowing that positive energy balance can be stored as TG in adipose tissue, a process called lipogenesis. In contrast, the mobilization of fat in adipocytes occurs through the hydrolysis of TG by hormone sensitive lipase (HSL), a phenomenon called lipolysis. At the center of this interface lipolysis and lipogenesis is the insulin hormone, which exerts a potent inhibitory role on the HSL, allowing lower rates of lipolysis and hence, highest fat mass [1]. However, adipose tissue is not only a passive stock organ of triacylglycerol, being currently recognized as an endocrine organ with multiple functions [1, 2]. Produces several biologically active substances called adipokines, among them tumor necrosis factor- (TNF-), monocyte chemoattractant protein 1 (MCP-1), interleukin-6 (IL-6), leptin, resistin and adiponectin. These substances actively participate in, among others, body energy regulation, mainly, by endocrine, paracrine and autocrine signals, which allow the adipocyte play a metabolic role in other tissues [3-5].

The aim of this study was to determine thyroid hormone (TH) profile in postmenopausal patients with breast cancer (BC).12 CaM patients stages I or II, without interventions that could interfere with tumor progression were selected, as well as and a control group with 18 postmenopausal women without CaM. We measured serum anti-thyroperoxidase antibody (TPOAB), thyroid-stimulating hormone (TSH), free thyroxine (T4L), estradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH), before and after surgery, besides immunohistochemistry for estrogen (ER) and progesterone (PR) receptors.Four patients with CaM showed changes in thyroid hormone profile: two had hyperthyroidism, one hypothyroidism, and one was positive for TPO-AB. All of them positive for ER and PR. TSH levels in breast cancer patients were not different from levels found in the control group (1.89 ± 1.56 vs. 2.86 ± 3.12 mIU/mL), but the levels of T4L in patients with CaM were statistically higher than those of the control group (1.83 ± 0.57 vs. 1.10 ± 0.20 ng/dL).These results reinforce the need for assessment of thyroid status in CaM patients, since in the absence of E2, changes in clinical HTs can act in E2-controlled processes.

There are several breast cancer experimental models including cell lines, which are commonly used due to ease of handling and storage. However, the continued propagation of cell lines and distribution among laboratories results in genetic drift and distancing from the in-vivo model. Primary organ culture of breast cancer slices may produce biological responses with high standard deviation for different samples, reflecting the heterogeneity of different tumors. Thus, the organ culture model system offers a new perspective to the results obtained in the cell lines and offers an alternative for studies that seek to individualize treatment for each patient, an increasingly prominent concern in current cancer therapy.

Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:26:51Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:31:39Z : No. of bitstreams: 1 2-s2.0-84862333929.pdf: 1588872 bytes, checksum: d84eef3b9c43a00d6f4a6b79900182ab (MD5) Made available in DSpace on 2014-05-27T11:26:51Z (GMT). No. of bitstreams: 0 Previous issue date: 2012-06-21 Aims. To analyze the influence of hyperthyroidism on the gene expression and serum concentration of leptin, resistin, and adiponectin in obese animals. Main Methods. Male Wistar rats were randomly divided into two groups: control (C)fed with commercial chow ad libitumand obese (OB)fed with a hypercaloric diet. After group characterization, the OB rats continued receiving a hypercaloric diet and were randomized into two groups: obese animals (OB) and obese with 25g triiodothyronine (T3)/100BW (OT). The T3 dose was administered every day for the last 2 weeks of the study. After 30 weeks the animals were euthanized. Samples of blood and adipose tissue were collected for biochemical and hormonal analyses as well as gene expression of leptin, resistin, and adiponectin. Results. T3 treatment was effective, increasing fT3 levels and decreasing fT4 and TSH serum concentration. Administration of T3 promotes weight loss, decreases all fat deposits, and diminishes serum levels of leptin, resistin, and adiponectin by reducing their gene expression. Conclusions. Our results suggest that T3 modulate serum and gene expression levels of leptin, resistin, and adiponectin in experimental model of obesity, providing new insights regarding the relationship between T3 and adipokines in obesity. Copyright © 2012 Renata de Azevedo Melo Luvizotto et al. Department of Internal Medicine Botucatu School of Medicine University of São Paulo State, 18618-000 Botucatu, SP Department of Sports Center of Physical Education and Sports Federal University of Espirito Santo (UFES), 29075-910 Vitória, ES

Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2013-08-22T18:41:21Z No. of bitstreams: 1 S0066-782X2011000900008.pdf: 317389 bytes, checksum: 050fa42a7102f7f1c3eac2678f8a8138 (MD5) Made available in DSpace on 2013-08-22T18:41:21Z (GMT). No. of bitstreams: 1 S0066-782X2011000900008.pdf: 317389 bytes, checksum: 050fa42a7102f7f1c3eac2678f8a8138 (MD5) Previous issue date: 2011-07-01 Made available in DSpace on 2013-09-30T19:27:50Z (GMT). No. of bitstreams: 2 S0066-782X2011000900008.pdf: 317389 bytes, checksum: 050fa42a7102f7f1c3eac2678f8a8138 (MD5) S0066-782X2011000900008.pdf.txt: 43869 bytes, checksum: 776bf0fb95907daa85e4d92e05ccaa4f (MD5) Previous issue date: 2011-07-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T15:07:41Z No. of bitstreams: 2 S0066-782X2011000900008.pdf: 317389 bytes, checksum: 050fa42a7102f7f1c3eac2678f8a8138 (MD5) S0066-782X2011000900008.pdf.txt: 43869 bytes, checksum: 776bf0fb95907daa85e4d92e05ccaa4f (MD5) Made available in DSpace on 2014-05-20T15:07:41Z (GMT). No. of bitstreams: 2 S0066-782X2011000900008.pdf: 317389 bytes, checksum: 050fa42a7102f7f1c3eac2678f8a8138 (MD5) S0066-782X2011000900008.pdf.txt: 43869 bytes, checksum: 776bf0fb95907daa85e4d92e05ccaa4f (MD5) Previous issue date: 2011-07-01 FUNDAMENTO: Treinamento físico (TF) aumenta a sensibilidade dos hormônios tireoidianos (HT) e a expressão gênica de estruturas moleculares envolvidas no movimento intracelular de cálcio do miocárdio, enquanto a restrição alimentar (RIA) promove efeitos contrários ao TF. OBJETIVO: Avaliar os efeitos da associação TF e RIA sobre os níveis plasmáticos dos HT e a produção de mRNA dos receptores HT e estruturas moleculares do movimento de cálcio do miocárdio de ratos. MÉTODOS: Utilizaram-se ratos Wistar Kyoto divididos em: controle (C, n = 7), RIA (R50, n = 7), exercício físico (EX, n = 7) e exercício físico + RIA (EX50, n = 7). A RIA foi de 50% e o TF foi natação (1 hora/dia, cinco sessões/semana, 12 semanas consecutivas). Avaliaram-se as concentrações séricas de triiodotironina (T3), tiroxina (T4) e hormônio tireotrófico (TSH). O mRNA da bomba de cálcio do retículo sarcoplasmático (SERCA2a), fosfolamban (PLB), trocador Na+/Ca+2 (NCX), canal lento de cálcio (canal-L), rianodina (RYR), calsequestrina (CQS) e receptor de HT (TRα1 e TRβ1) do miocárdio foram avaliados por reação em cadeia da polimerase (PCR) em tempo real. RESULTADOS: RIA reduziu o T4, TSH e mRNA do TRα1 e aumentou a expressão da PLB, NCX e canal-L. TF aumentou a expressão do TRβ1, canal-L e NCX. A associação TF e RIA reduziu T4 e TSH e aumentou o mRNA do TRβ1, SERCA2a, NCX, PLB e correlação do TRβ1 com a CQS e NCX. CONCLUSÃO: Associação TF e RIA aumentou o mRNA das estruturas moleculares cálcio transiente, porém o eixo HT-receptor não parece participar da transcrição gênica dessas estruturas. BACKGROUND: Chronic exercise and food restriction (FR) have directionally opposite changes in transcription of molecular structures of calcium handling and thyroid hormone (TH) status. OBJECTIVE: Evaluate the association of chronic exercise and FR on serum thyroid hormones and gene transcription of molecular structures of intracellular calcium transients and thyroid receptors in myocardium of rats. METHODS: Male Wistar Kyoto rats, divided into two groups: control (C, n = 7), FR (R50, n = 7), chronic exercise (EX, n = 7) and chronic exercise + FR (EX50, n = 7). FR was of 50% and exercise was swimming (1 hour/day, 5 days/week, during 12 weeks). Serum concentrations of T3, T4 and TSH were determined. The mRNA gene expression of the sarcoplasmatic reticulum calcium pump (SERCA2a), phospholamban (PLB), Na+/Ca+2 exchanger (NCX), calcium channel L-type (L-channel), ryanodine (RYR), calsequestrin (CQS) and HT receptor (TRα1 and TRβ1) of the myocardium was performed by PCR real-time. RESULTS: FR reduced serum levels of T4 and TSH and TRα1 mRNA and increased the expression of PLB, NCX and L-channel. Exercise increased the TRβ1 receptor, L-channel and NCX. The association of exercise and FR reduced plasma T4 and TSH, TRβ1 mRNA increase, SERCA2a, NCX and PLB, and there was a significant correlation of TRβ1 with CQS and NXC. CONCLUSION: Chronic exercise and food restriction increased the mRNA of transient Ca2+ proteins; however, TH-receptor axis cannot participate in the transcription of mRNA of myocardial calcium transient proteins. FUNDAMENTO: Entrenamiento físico (EF) aumenta la sensibilidad de las hormonas tiroideas (HT) y la expresión génica de estructuras moleculares envueltas en el movimiento intracelular de calcio del miocardio, mientras que la restricción alimenticia (RA) promueve efectos contrarios al EF. OBJETIVO: Evaluar los efectos de la asociación EF y RA sobre los niveles plasmáticos de los HT y la producción de ARNm de los receptores HT y estructuras moleculares del movimiento de calcio del miocardio de ratones. MÉTODOS: Se utilizaron ratones Wistar Kyoto divididos en: control (C, n = 7), RA (R50, n = 7), ejercicio físico (EX, n = 7) y ejercicio físico + RA (EX50, n = 7). La RA fue de 50% y el EF fue natación (1 hora/día, cinco sesiones/semana, 12 semanas consecutivas). Se evaluaron las concentraciones séricas de triyodotironina (T3), tiroxina (T4) y hormona tireotrófico (TSH). El ARNm de la bomba de calcio del retículo sarcoplasmático (SERCA2a), fosfolamban (PLB), intercambiador Na+/Ca+2 (NCX), canal lento de calcio (canal-L), rianodina (RYR), calsequestrina (CQS) y receptor de HT (TRα1 y TRβ1) del miocardio fueron evaluados por reacción en cadena de la polimerasa (PCR) en tiempo real. RESULTADOS: RA redujo el T4, TSH y ARNm del TRα1 y aumentó la expresión de la PLB, NCX y canal-L. EF aumentó la expresión del TRβ1, canal-L y NCX. La asociación EF y RA redujo T4 y TSH y aumentó el ARNm del TRβ1, SERCA2a, NCX, PLB y correlación del TRβ1 con la CQS y NCX. CONCLUSIÓN: Asociación EF y RA aumentó el ARNm de las estructuras moleculares calcio transiente, sin embargo el eje HT-receptor no parece participar de la transcripción génica de esas estructuras. Universidade Federal de Mato Grosso Instituto de Ciências da Saúde Universidade Estadual Paulista Faculdade de Medicina Universidade Estadual Paulista Faculdade de Medicina

Previous studies have shown that food restriction promotes myocardial dysfunction in rats. However, the molecular mechanisms that are responsible are unclear. We investigated the role of sarcoplasmic reticulum Ca2+-ATPase (SERCA2) on myocardial performance in food-restricted rats. Male Wistar–Kyoto rats, 60 days old, were fed a control or restricted diet (daily energy intake reduced to 50% of the control) for 90 days. Expression of Serca2a, phospholamban (PLB), Na+/Ca2+ exchanger (NCX), and thyroid hormone receptor (TRα1, TRβ1) mRNA was determined by quantitative PCR. SERCA2 activity was measured by using 20 µmol/L cyclopiazonic acid (CPA) in a left ventricular papillary muscle preparation during isometric contraction in basal conditions and during post-rest contraction. Serum concentrations of thyroxine (T4) and thyrotropin (TSH) were also determined. The 50%-restricted diet reduced body and ventricular weight and serum T4 and TSH levels. The interaction of CPA and food restriction reduced peak developed tension and maximum rate of tension decline (–dT/dt), but increased the resting tension intensity response during post-rest contraction. PLB and NCX mRNA were upregulated and TRα1 mRNA was downregulated by food restriction. These results suggest that food restriction promotes myocardial dysfunction related to impairment of sarcoplasmic reticulum Ca2+ uptake as a result of a hypothyroid state.

Objectives: To examine the effects of triiodothyronine (T3), 17β-estradiol (E2), and tamoxifen (TAM) on transforming growth factor (TGF)-α gene expression in primary breast cancer cell cultures and interactions between the different treatments. Methods and results: Patients included in the study (no.=12) had been newly diagnosed with breast cancer. Fresh human breast carcinoma tissue was cut into 0.3-mm slices. These slices were placed in six 35-mm dishes on 2-ml organ culture medium. Dishes received the following treatments: dish 1: ethanol; dish 2: T3; dish 3: T3+TAM; dish 4: TAM; dish 5: E2; dish 6: E2+TAM. TGF-α mRNA content was normalized to glyceraldehyde-3-phosphate dehydrogenase mRNA levels. All tissues included in this study were positive for estrogen receptor (ER) and thyroid hormone receptor expression. Treatment with T3 for 48 h significantly increased TGF-α mRNA levels compared to controls (15-fold), and concomitant treatment with TAM reduced expression to 3.4-fold compared to controls. When only TAM was added to the culture medium, TGF-α mRNA expression increased 5.3-fold, significantly higher than with all other treatment modalities. Conclusion: We demonstrate that TGF-α mRNA expression is more efficiently upregulated by T3 than E2. Concomitant treatment with TAM had a mitigating effect on the T3 effect, while E2 induced TGF-α upregulation. Our findings show some similarities between primary culture and breast cancer cell lines, but also some important differences: a) induction of TGF-α, a mitogenic protein, by TAM; b) a differential effect of TAM that may depend on relative expression of ER α and β; and c) supraphysiological doses of T3 may induce mitogenic signals in breast cancer tissue under conditions of low circulating E2.

Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2013-08-22T18:59:49Z No. of bitstreams: 1 S0004-27302007000900008.pdf: 96437 bytes, checksum: 5c4bdd1d5d17b3cd7e07afe6bdf9f76e (MD5) Made available in DSpace on 2013-08-22T18:59:49Z (GMT). No. of bitstreams: 1 S0004-27302007000900008.pdf: 96437 bytes, checksum: 5c4bdd1d5d17b3cd7e07afe6bdf9f76e (MD5) Previous issue date: 2007-12-01 Made available in DSpace on 2013-09-30T19:57:11Z (GMT). No. of bitstreams: 2 S0004-27302007000900008.pdf: 96437 bytes, checksum: 5c4bdd1d5d17b3cd7e07afe6bdf9f76e (MD5) S0004-27302007000900008.pdf.txt: 19752 bytes, checksum: 6789083165b81218f2b3db6d2e17f82b (MD5) Previous issue date: 2007-12-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T15:14:51Z No. of bitstreams: 2 S0004-27302007000900008.pdf: 96437 bytes, checksum: 5c4bdd1d5d17b3cd7e07afe6bdf9f76e (MD5) S0004-27302007000900008.pdf.txt: 19752 bytes, checksum: 6789083165b81218f2b3db6d2e17f82b (MD5) Made available in DSpace on 2014-05-20T15:14:51Z (GMT). No. of bitstreams: 2 S0004-27302007000900008.pdf: 96437 bytes, checksum: 5c4bdd1d5d17b3cd7e07afe6bdf9f76e (MD5) S0004-27302007000900008.pdf.txt: 19752 bytes, checksum: 6789083165b81218f2b3db6d2e17f82b (MD5) Previous issue date: 2007-12-01 Dois pacientes índices da família analisada neste estudo foram submetidos a adrenalectomia bilateral devido a feocromocitoma. Foi, então, realizado o estudo genético dos pacientes e de sete parentes de primeiro grau. Os dois pacientes com feocromocitoma e dois outros membros assintomáticos da família apresentaram a mutação c496G>T no exon 3 do gene VHL. A família perdeu seguimento médico. Três anos após a realização da avaliação genética, a irmã dos pacientes, portadora da mutação, foi encaminhada para o nosso serviço após uma gestação complicada por pré-eclampsia. Ela referia paroxismos sugestivos de feocromocitoma, mas as metanefrinas urinárias eram negativas. Entretanto, a tomografia computadorizada de abdômen evidenciou uma massa adrenal que também se contrastou na cintilografia com metaiodobenzilguanidina (MIBG). Esse estudo mostra que a análise molecular do paciente índice pode levar à identificação de parentes assintomáticos portadores da mutação. Além disso, mesmo com as metanefrinas urinárias negativas, a identificação de uma mutação específica levou a um aumento da suspeita e detecção de feocromocitoma na irmã dos afetados pela doença. The two index patients of the family analyzed in this study had undergone bilateral adrenalectomy for pheochromocytomas. This prompted genetic analyses of the probands and seven first-degree relatives. The two pheochromocytoma patients and two additional asymptomatic family members were found to harbor a mutation c496G>T in exon 3 of the VHL gene. The family was then lost to systematic follow-up. Three years after performing the initial genetic evaluation, the sister of the probands, who was known to carry the same VHL germline mutation, was referred to our service after a pregnancy that was complicated by preeclampsia. She reported paroxysms suggestive for pheochromocytoma, but her urinary metanephrines were negative. However, computerized tomography of the abdomen showed an adrenal mass that was also positive on metaiodobenzylguanidine (MIBG) scintigraphy. This study illustrates that molecular analysis of the index patient(s) can lead to the identification of presymptomatic relatives carrying the mutation. Moreover, despite negative urinary metanephrines, the identification of a specific mutation has led to an increased suspicion and detection of a pheochromocytoma in the sister of the probands. Universidade Estadual Paulista Faculdade de Medicina Departamento de Clínica Médica Northwestern University Division of Endocrinology, Metabolism, and Molecular Medicine Universidade Estadual Paulista Faculdade de Medicina Departamento de Clínica Médica

Bone tumor incidence in women peaks at age 50-60, coinciding with the menopause. That estrogen (E2) and triiodothyronine (T3) interact in bone metabolism has been well established. However, few data on the action of these hormones are available. Our purpose was to determine the role of E2 and T3 in the expression of bone activity markers, namely alkaline phosphatase (AP) and receptor activator of nuclear factor kappaB ligand (RANKL). Two osteosarcoma cell lines: MG-63 (which has both estrogen (ER) and thyroid hormone (TR) receptors) and SaOs-29 (ER receptors only) were treated with infraphysiological E2 associated with T3 at infraphysiological, physiological, and supraphysiological concentrations. Real-time RT-PCR was used for expression analysis. Our results show that, in MG-63 cells, infraphysiological E2 associated with supraphysiological T3 increases AP expression and decreases RANKL expression, while infraphysiological E2 associated with either physiological or supraphysiological T3 decreases both AP and RANKL expression. On the other hand, in SaOs-2 cells, the same hormone combinations had no significant effect on the markers' expression. Thus, the analysis of hormone receptors was shown to be crucial for the assessment of tumor potential growth in the face of hormonal changes. Special care should be provided to patients with T3 and E2 hormone receptors that may increase tumor growth.

Univ Sao Paulo State, UNESP, Dept Clin Med, Botucatu Sch Med, BR-18618000 Botucatu, SP, Brazil

Our last research showed that association of physical training (PT) and food restriction (FR) increases inotropic myocardial contractile response in rats.PURPOSE: To test the hypothesis that myocardial contractile response improvement in PT and FR rats is related to increase in the intracellular cal